Percutaneous transluminal coronary angioplasty (PTCA) is a procedure for treating heart disease. A physician introduces a catheter assembly, having a balloon portion, percutaneously into the cardiovascular system of a patient via the brachial or femoral artery. The physician advances the catheter assembly through the coronary vasculature until the balloon portion crosses the occlusive lesion. Once in position, the physician inflates the balloon to radially compress the atherosclerotic plaque of the lesion and remodel the vessel wall. The surgeon then deflates the balloon to remove the catheter.
However, this procedure can create intimal flaps and tear arterial linings, which can collapse and occlude the vessel after balloon removal. Moreover, thrombosis and restenosis of the artery may develop over several months following the procedure, which may require another angioplasty procedure or a by-pass operation. To reduce arterial occlusion, thrombosis, and restenosis, the physician can implant a stent into the vessel.
Physicians use stents mechanically and to provide biological therapy. Mechanically, stents act as scaffoldings, physically holding open and, if desired, expanding the vessel wall. Typically, stents compress for insertion through small vessels and then expand to a larger diameter once in position. U.S. Pat. No. 4,733,665, issued to Palmaz; U.S. Pat. No. 4,800,882, issued to Gianturco; and U.S. Pat. No. 4,886,062, issued to Wiktor disclose examples of PTCA stents.
Medicating the stent provides for pharmacological therapy. Medicated stents allow local drug administration at the diseased site. To provide an effective drug concentration at a site, systemic treatment often requires concentrations that produce adverse or toxic effects. Local delivery advantageously allows for smaller systemic drug levels in comparison to systemic treatment. Because of this, local delivery produces fewer side effects and achieves results that are more favorable. One proposed method for medicating stents involves coating a polymeric carrier onto a stent surface. This method applies a solution that includes a solvent, a dissolved polymer, and a dissolved or dispersed drug to the stent. As the solvent evaporates, it leaves a drug-impregnated polymer coating on the stent.
Current biomaterials research aims at controlling protein adsorption on implantable medical devices. Current biomaterials typically exhibit uncontrolled protein adsorption, leading to a mixed layer of partially denatured proteins. Current surfaces contain different cell binding sites resulting from adsorbed proteins such as fibrinogen and immunoglobulin G. platelets and inflammatory cells such as macrophages and neutrophils adhere to these surfaces. When activated, these cells secret a wide variety of pro-inflammatory and proliferative factors. Non-fouling surfaces control these events, and absorb little or no protein, primarily due to their hydrophilicity. One prior art approach creates these surfaces by using hyaluronic acid or polyethylene glycol. Non-fouling surfaces or coatings are a subset of biobeneficial coatings, which are coatings that benefit the treatment site without necessarily releasing pharmaceutically or therapeutically active agents (“drug(s)”). Another type of biobeneficial coating contains free-radical scavengers, which preserve nitric oxide and prevent oxidative damage.
Biobeneficial coatings provide surfaces that can have a biological benefit without the release of pharmaceutically active agents. Although an otherwise biobeneficial coating could release such active agents, if that were desired. The world of biobeneficial coatings may be divided into two categories, those that are intended to be bioabsorbable, and those that are intended to be biostable. Desirable properties for bioabsorbable, biobeneficial coatings include any of the following properties:
Improved bioactivity in-vitro and in-vivo, measured by                platelet adhesion        protein binding        inflammatory response        acceleration of healing        
Improved mechanical properties, measured by                minimal cracking on expansion        resistance to damage from crimping and heat and pressure stent-catheter attachment processes        balloon shear resistance        
Improved bioabsorption rate, measured by                slow enough degradation to minimize inflammatory response        slow enough degradation to capture some biobeneficial benefit        fast enough degradation to substantially completely degrade in an accessible time (preferably less than 6 months)        
One suitable polymer family useful with medical devices is polyurethanes. Polyurethanes are a broad family of elastomeric materials. A subset of these materials, thermoplastic elastomers, has served in medical devices for decades. Polymer properties, such as flexibility, high elongation, fatigue resistance, and blood compatibility, have driven polyurethane medical applications. A current topic in drug eluting stents is polymeric coatings that hold the drug, control its release, and bioabsorb with little or no inflammatory response. Polyurethanes are not usually considered bioabsorbable polymers because they contain a hydrolytically stable urethane linkage. While physiologic enzymes can cleave the urethane linkage, there is no evidence that this leads to complete bioabsorption. (G. L. Y. Woo et al. Biomaterials 21 (2000) 1235-1246.)
Moreover, urethane cleavage in aromatic-diisocyanate-based polyurethanes releases aromatic diamines, which can be carcinogenic. Using diisocyanates that would degrade to endogenous diamines or fragments that are identical to or similar to endogenous diamines avoids aromatic diamine release. Along those lines, Wagner has taken steps to develop bioabsorbable polyurethanes. (J. Guan, M. S. Sacks, E. J. Beckman, W. R. Wagner, J. Biomat. Res. 2002, 493-503.) Ways to improve their biocompatibility, modify the drug release rate via increased hydrophilicity, and increase their number and type are described below. Incorporating hydrolytically labile groups into the polymer backbone alters polyurethane biodegradability. Esters are an example of hydrolytically labile groups that may be incorporated into the polyurethane polymer backbone.